No abstract

Ketoconazole, an orally active antimycotic drug, is a potent inhibitor of ergosterol biosynthesis in Candida albicans when added to culture media which support yeast or mycelial growth or to cultures containing outgrown mycelium. This inhibition coincides with accumulation of sterols with a methyl group at C-14 and can thus be attributed to an interference with one of the reactions involved in the removal of the 14 alpha-methyl group of lanosterol. When administered to rats infected with C. albicans, ketocanazole also inhibits fungal synthesis of ergosterol. A six-times-higher dose is required to effect cholesterol synthesis by rat liver.

604th MEETING, CAMBRIDGE 665 known as denmert) caused total loss of its fungicidal activity towards Sphaerotheca fuliginea and Monilinia fmctigena. These workers suggested that the co-ordination of the heterocyclic meta-nitrogen atom of buthiobate to a cationic receptor site may be important for its fungicidal activity. The cationic receptor site mentioned would appear to be the Fez+ of the cytochrome P-450 catalysing step 1 of the sterol 14-demethylation sequence.

No abstract

Cytochrome P-450: Target for itraconazole. Drug Dev. Res. 8:287-298, 1986.The N-substituted triazole, itraconazole, has high affinity for the cytochrome P-450 (cyt. P-450) isozyme involved in the 14a-demethylation of lanosterol in Candida albicans microsomes. Fifty per cent inhibition was already observed at itraconazole concentations < 5x lo-' M. Higher concentrations (> lo-' M) of this antifungal are needed to interfere with the 14 a-demethylation in mammalian cells. Unlike ketoconazole, itraconazole does not significantly affect in vitro androgen, gluco-and mineralocorticoid steroidogenesis. ltraconazole also does not affect the cyt. P-450-dependent 19-hydroxylation of testosterone, a step in the conversion of androgens to estrogens. The l-hydroxylation of testosterone by pig testes microscomes is only slightly inhibited. It is hypothesized that itraconazole's selective activity on ergosterol biosynthesis is due to its high affinity for the apoprotein of the C. albicans cyt. P-450 involved in the 1401-demethylation of lanosterol.